Transient abnormal myelopoiesis, myelodysplastic syndrome and acute myeloid leukemia in children with Down syndrome

Myeloid neoplasms associated with Down syndrome (DS) are represented by transient abnormal myelopoiesis, acute myeloid leukemia (AML) and myelodysplastic syndrome. Transient abnormal myelopoiesis is a clonal myeloproliferative syndrome characterized by an increased number of blast cells in the peripheral blood, morphologically and immunophenotypically most commonly related to megakaryoblasts, and the presence of an acquired mutation in the GATA1 gene. This syndrome occurs in infants up to 6 months of age. Children with DS have an abnormally high risk of developing hematological malignancies. The incidence of AML in these patients is 150–400 times higher than in children without DS. Survival rates and prognosis in children with AML and DS (AML-DS) treated with reduced-intensity chemotherapy are significantly higher than in children without DS: the overall survival ranges from 84% to 90% and the event-free survival is up to 89%. At the same time, standard intensive chemotherapy (with high-dose anthracyclines and intensive timing of induction) is associated in these patients with high toxicity and significant mortality due to infectious complications. Treatment outcomes in patients with AML-DS in Russia do not exceed 66%, which is significantly lower than those achieved by international cancer research groups. There is a need for standardization of therapy for AML-DS in Russia and introduction of a uniform treatment protocol with reduced chemotherapy doses and common standards of supportive care as well as prophylaxis and treatment of infectious complications. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of Russia.